Premium
Effect of Cinacalcet Hydrochloride, a New Calcimimetic Agent, on the Pharmacokinetics of Dextromethorphan: In Vitro and Clinical Studies
Author(s) -
Nakashima Daisuke,
Takama Hirotaka,
Ogasawara Yuko,
Kawakami Tetsuyoshi,
Nishitoba Tsuyoshi,
Hoshi Sakuo,
Uchida Eiji,
Tanaka Hideji
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007304103
Subject(s) - cinacalcet , pharmacology , dextromethorphan , quinidine , pharmacokinetics , drug interaction , chemistry , medicine , cyp3a4 , secondary hyperparathyroidism , calcium , parathyroid hormone , cytochrome p450 , metabolism
Cinacalcet hydrochloride (cinacalcet) is a positive allosteric modulator of the calcium‐sensing receptor indicated for the treatment of secondary hyperparathyroidism in dialysis patients. In vitro study has demonstrated that cinacalcet is a potent inhibitor of cytochrome P450 (CYP) 2D6 with a K i value of 0.087 μmol/L, which is comparable to the well‐known potent CYP2D6 inhibitor, quinidine (0.064 μmol/L). A clinical study was conducted to assess the inhibitory effect of cinacalcet on CYP2D6 substrates in healthy volunteers. Each subject received 50 mg of cinacalcet or a matched placebo orally once daily for 8 days with 30 mg of dextromethorphan coadministered on day 8. The mean AUC 0‐∞ and C max of dextromethorphan increased 11‐ and 7‐fold, respectively, in extensive metabolizers when coadministered with cinacalcet versus placebo. Therefore, during concomitant treatment with cinacalcet, it may be necessary to consider making dose adjustments for drugs with a narrow therapeutic index that are mainly metabolized by CYP2D6.